We propose a cluster-randomized trial to assess the impact of community-based DOT-HAART on HIV-positive individuals and community members in Lima, Peru. We will enroll individuals living in extreme poverty who are starting either first-line HAART or salvage therapy due to virologic failure. Those residing in intervention clusters will receive 12 months of DOT-HAART. We aim to 1) assess the proportion with suppressed HIV viral load at 18 and 24 months after starting HAART among those receiving community-based DOT-HAART versus the control group; 2) compare social capital among community members in DOT-HAART versus control communities; and 3) assess the cost-effectiveness of community-based DOT-HAART. Innovative aspects of this proposal include 1) a targeted intervention for the most vulnerable subgroup of individuals starting HAART (i.e. those living in extreme poverty); 2) a community- based DOT-HAART intervention designed specifically to achieve long-term efficacy; 3) cost- effectiveness analysis; and 4) assessment of the intervention effect on community-level social capital. These study components will inform how best to design and implement DOT-HAART strategies in Peru and other resource-poor settings. By offering a practical, efficacious and cost-effective model of DOT-HAART for resource-poor settings, the findings of this study could improve global efforts to achieve excellent long-term clinical outcomes among individuals on HAART. PUBLIC HEALTH RELEVANCE: Given the limited resources and magnitude of human immunodeficiency virus (HIV) treatment scale-up in resource-poor countries, cost-effective, efficacious adherence interventions for resource-poor settings are urgently needed. Despite accumulating evidence that directly observed therapy of highly active antiretroviral therapy (DOT- HAART) is effective, how best to apply DOT-HAART in resource-poor settings remains unanswered. Development of DOT-HAART interventions with long-term efficacy, refinement of target populations, and evaluation of cost-effectiveness are all scientific research priorities that are urgently needed to inform efforts to implement DOT-HAART in settings with limited resources.